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Functional differences between influenza A-specific cytotoxic T lymphocyte clones expressing dominant and subdominant TCR

Lawson, Thomas, Man, Stephen Tzekwung, Wang, Edward Chung Yern, Williams, Sheila, Amos, Nick, Gillespie, Geraldine M., Moss, Paul A. and Borysiewicz, Leszek K. 2001. Functional differences between influenza A-specific cytotoxic T lymphocyte clones expressing dominant and subdominant TCR. International Immunology 13 (11) , pp. 1383-1390. 10.1093/intimm/13.11.1383

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We have shown that the dominance of CD8+ T cells expressing TCR Vβ17 in the adult HLA-A*0201-restricted influenza A/M158–66-specific response is acquired following first antigen exposure. Despite the acquired dominance of Vβ17+ cells, subdominant M158–66-specific clones expressing non-Vβ17+ TCR persist in all individuals. To determine whether the affinity of the expressed TCR for the HLA-A*0201/M158–66 complex could influence functional properties, M158–66-specific clones expressing subdominant (non-Vβ17+) TCR were compared to cytotoxic T lymphocyte (CTL) clones expressing dominant (Vβ17+) TCR. The Vβ17+ CTL required up to 10,000-fold lower amounts of M1 peptide to mediate lysis compared to CTL clones expressing other Vβ gene segments. All Vβ17+ CTL clones tested bound HLA-A*0201/M158–66 tetramer, but two of three CTL clones expressing other TCR did not bind tetramer. The inability of non-Vβ17+ CTL to bind tetramer did not correlate with phenotype, CD8 dependence or with cytokine production profiles. This suggests a limitation for the use of tetramers in examining subdominant T cell responses. Together these findings suggest that Vβ17+ CTL which dominate the HLA-A*0201-restricted CTL response against influenza A are not functionally distinct from subdominant non-Vβ17+ CTL. The dominance of Vβ17+ CTL is likely to result from a competitive advantage due to superior CTL avidity for the HLA-A*0201/M158–66 complex.

Item Type: Article
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: cytotoxic T lymphocyte; Infectious immunity virus; Human repertoire development; TCR
Publisher: Oxford University Press
ISSN: 1460-2377
Funders: MRC, ARC, Royal Society
Last Modified: 11 Jul 2022 08:08

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